Lymphatic Function in Patients With a Fontan-Kreutzer Circulation

The Lymphatic Morphology and Function of Fontan-Kreutzer Operated Patients

The lymphatics regulate the interstitial fluid by removing excessive fluid. It represents an extremely important step in the prevention of edema. The Fontan-Kreutzer procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy (PLE) and peripheral edema that may involve the lymphatic circulation.

Our hypothesis is that patients with a univentricular circulation have a reduced functionality of the lymphatic vasculature, which predisposes them to developing complications such as edema and PLE.

The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF. The anatomy is described using non-contrast MRI and the capillary filtration rate is measured using plethysmography.

Study Overview

• Status: Unknown
• Conditions: Univentricular Heart; Lymphatic Abnormalities; Lymphatic Edema
• Intervention / Treatment: Diagnostic test: Near Infrared Fluorescence Imaging; Diagnostic test: Non-contrast MRI; Diagnostic test: Strain Gauge Plethysmography

Detailed Description

Background:

The lymphatics regulate the interstitial fluid by removing excessive fluid. It represents an extremely important step in the prevention of edema. The Fontan-Kreutzer procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy (PLE) and peripheral edema that may involve the lymphatic circulation.

Hypothesis:

Patients with a univentricular circulation have a reduced functionality of the lymphatic vasculature, which predisposes them to developing complications such as edema and PLE.

Material and Methods:

The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF. The anatomy is described using non-contrast MRI and the capillary filtration rate is measured using plethysmography. The study population is patients with Fontan-Kreutzer circulation operated at Aarhus University hospital. Exclusion criteria is BMI>30 and age (years) < 18. The Fontan-Kreutzer group will be compared with an age, gender and weight matched control group of healthy volunteers.

• Study Type: Observational
• Enrollment (Actual): 10

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients born with an univentricular heart, who surgically is corrected with a Fontan-Kreutzer Circulation

Description

Inclusion Criteria:

• Fontan-Kreutzer circulation

Exclusion Criteria:

• BMI>30,
• Age<18
• Mental illness

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fontan-Kreutzer operated patients; Patients with a Fontan-Kreutzer circulation. No interventions are done. (The intervention is the operation done 15-20 years ago)	Diagnostic test: Near Infrared Fluorescence Imaging; The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF.; Other Names: Strain-Gauge Plethysmography; Diagnostic test: Non-contrast MRI; The anatomy is described using non-contrast MRI.; Diagnostic test: Strain Gauge Plethysmography; The capillary filtration rate is measured using plethysmography
Healthy Control subjects; Age, gender and weight matched control subjects	Diagnostic test: Near Infrared Fluorescence Imaging; The functional state of lymphatics is investigated using near infrared fluorescence imaging, NIRF.; Other Names: Strain-Gauge Plethysmography; Diagnostic test: Non-contrast MRI; The anatomy is described using non-contrast MRI.; Diagnostic test: Strain Gauge Plethysmography; The capillary filtration rate is measured using plethysmography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pumping pressure	Occlusion of lymphatic flow by inflating a cuff (Hokanson E20 Rapid cuff inflator, Hokanson AG101 air source) to 70mmHg and then reducing the pressure with 5mmHg each 5th minute. The highest pressure under which the fluorescent dye is able to cross the inflatable cuff is labelled Ppump.	1 hour
Contraction Frequency	Contraction frequency in vessels in the main drainage pathway of the legs (ventromedial bundle) as well as vessels draining the area behind the medial malleolus.	6 min
Refill time	The time it takes for a 10 cm long vessel to refill after emptying the vessel with massage	20 min
Velocity	The velocity measured in cm/s for a packet of lymph moving from one region of interest (ROI) to another through atlas a 5 cm straight vessel	6 min
Capillary Filtration Rate	A 5-step 20-min venous congestion protocol will be used to measure capillary filtration. The capillary filtration rate (µl·100 ml-1 ·min-1 ) is measured as the slope of the time-volume change (%) curve at steady state at the end of each pressure phase.	25 min

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Vibeke E Hjortdal, MD, PhD, Dr.Med, Aarhus University Hospital, Department of Cardiothoracic and Vascular Surgery

Publications and helpful links

General Publications

• Mohanakumar S, Telinius N, Kelly B, Lauridsen H, Boedtkjer D, Pedersen M, de Leval M, Hjortdal V. Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation. Circ Cardiovasc Imaging. 2019 Apr;12(4):e008074. doi: 10.1161/CIRCIMAGING.118.008074.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2014
• Primary Completion (Actual): June 20, 2017
• Study Completion (Anticipated): August 31, 2018

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): December 20, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Lymphatic Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Univentricular Heart; Lymphatic Abnormalities
• Other Study ID Numbers: Fontan17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No